The news came as John Kerry arrived in Baghdad to discuss the United States' desire to build a military, political and financial coalition of nations to defeat Isis, which calls itself Islamic State, with the newly appointed Iraqi government in the capital.

Ahrar al-Sham has been the largest and strongest Islamist group fighting Isis - despite sharing similar salafist views - and has shown more moderate colours in recent months, causing particular distress to the rebels.

The meeting was taking place in an underground bunker known as "Base Zero", in the town of Ram Hamdan, close to Idlib in north-western Syria.

The bunker also housed a munitions store, raising both the possibility of a carefully planned operation or even a tragic accident.

The Syrian Observatory for Human Rights said the blast killed 28 of Ahrar al-Sham's commanders. Witnesses report seeing plumes of smoke, followed by chaos as the site was closed to allow for the retrieval of bodies.

According to sources within the Free Syrian Army (FSA), the Syrian Opposition's Ministry of Defence is treating the bombing as an attack on the revolution.

Former leader of Aleppo City Military Revolutionary Council, Colonel Abdul Jabbar Akaidi, condemned the attack, particularly given Ahrar al-Sham's recent turn towards the more moderate FSA.

"I'm shocked. I'm very sad for the martyrs of Ahrar al-Sham. They were trying to change from Salafi ideology to a more moderate form," he told The Independent.

"They announced that they want to work with the FSA and announced a fierce war against Isis. Their death is a big loss for the revolution and the war against the Islamic State."

According to sources in Idlib, a bomb went off inside the meeting itself, which ignited flammable toxic gases, causing many to suffocate.

Abu Baraa, a rebel figure from a group allied with Ahrar al-Sham, said a doctor who examined the bodies reported that they bore little visible sign of injury.

Conspiracy theories are already rife, but Isis and the Assad regime are the most obvious culprits. Isis jihadis were jubilant on Twitter at the news, although no group has claimed responsibility.

It would not be the first time Isis has been accused of assassinating a leader of Ahrar Al-Sham. In January another senior leader was killed in a suicide attack.

Abu Khaled al-Soury had fought alongside al-Qaeda founder Osama bin Laden and was close to its current chief, Ayman al-Zawahri. Isis denied involvement in the January attack.

The timing is particularly hurtful, as the group was entering talks with more moderate elements of the rebel fighters, despite its extreme history, which has seen it linked closely with al-Qaeda. Aron Lund, a contributing analyst for The Carnegie Endowment for International Peace and close follower of Ahrar al-Sham, said: "The gutting of Ahrar al-Sham's leadership will have major ripple effects in the opposition."

He added: "[The group was] a bridge between the hardcore salafists and more moderate groups and had a religious legitimacy that other groups don't have. [It] played a very important role in shaping the insurgency and really mattered in the US decision to arm the rebels."

US President Barack Obama is due to make a statement on America's involvement in the fight against Isis in Iraq and Syria.

He was expected to outline a broad expansion of the US military role in combating extremists, including a call for arming Syrian opposition forces and potentially launching airstrikes in both countries.

France said it would take part in military air action against Isis militants in Iraq if necessary, but said any action it takes against the group in Syria would take another form.

"The situation in Syria is different," Foreign Minister Laurent Fabius said in a speech in Paris. "We must act in both cases, but not with the same modalities."

Ahrar al-Sham, meanwhile, has already named its new leader as Abu Jaber Maskani (aka Sheikh Al-Hashami), a former FSA commander who has extensive experience in fighting Isis, having done so around the tribal area of Maskana.

In a video released on YouTube, the group's new leader eulogised the dead. "Jihadi men of our nation... do not let the crisis shake you or the calamity divide you," Abu Jaber said. "Rise, let us die for what they have died for."

The big question remains as to where the approximately 20,000-strong group will lay its allegiance or if it will unite behind its new leadership.

Many fear a portion of the fighters will join the ranks of Isis or Jabhat Al-Nusra, with whom they share a similar ideology, even if their leaders were attempting to come in line with moderate and western-backed factions.

For Colonel Abdul Jabbar Akaidi, the latest attack marks a new stage of the revolution, with leaders being picked off one-by-one.

"It definitely feels like we have entered the stage of eliminating the Syrian Revolutionary leaders through a very specific strategy of assassination," he said.